Saladin 5e Extended Outline

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Saladin A&P, 8e Extended Chapter Outline

Chapter 12 Nervous Tissue

I. Overview of the Nervous System (pp. 432–433)

A. The study of the nervous system is called neurobiology. (p. 432)

B. Two organ systems are dedicated to maintaining internal coordination—the endocrine system and the nervous system. (p. 432) (Fig. 12.1)

C. The nervous system carries out its coordinating task in three basic steps. (p. 433)

1. Through sense organs and simple nerve endings, it receives information about changes in the body and external environment and transmits messages to the spinal cord and

brain.

2. The spinal cord and brain process this information, relate it to past experience, and determine an appropriate response.

3. The spinal cord and brain issue commands to muscle and gland cells to carry out the response.

D. The nervous system has two major anatomical subdivisions: the central nervous system and peripheral nervous system; the latter has additional subdivisions. (pp. 432–433) (Fig. 12.2)

1. The central nervous system (CNS) consists of the brain and spinal cord, which are enclosed and protected by the cranium and vertebral column.

2. The peripheral nervous system (PNS) consists of all the nervous system except the brain and spinal cord; it is composed of nerves and ganglia.

a. A nerve is a bundle of nerve fibers (axons) wrapped in connective tissue. b. A ganglion (pl. ganglia) is a knotlike swelling in a nerve where the cell bodies of neurons are concentrated.

3. The PNS is functionally divided into sensory and motor divisions.

a. The sensory (afferent) division carries sensory signals from receptors to the

CNS; this pathway informs the CNS of stimuli.

i. The somatic sensory division carries signals from receptors in the skin, muscles, bones, and joints.

ii. The visceral sensory division carries signals from viscera of the thoracic and abdominal cavities.

b. The motor (efferent) division carries signals from the CNS to gland and muscle cells that carry out the body’s responses; cells and organs that respond are called effectors.

1

i. The somatic motor division carries signals to the skeletal muscles, producing muscular contractions that are under voluntary control as well as involuntary contractions called somatic reflexes.

ii. The visceral motor division (autonomic nervous system) carries signals to glands, cardiac muscle, and smooth muscle over which we have no voluntary control; the responses are termed visceral reflexes.

c. The autonomic nervous system has two further divisions.

i. The sympathetic division tends to arouse the body for action—for example, through accelerating the heartbeat and increasing respiratory airflow and inhibiting digestion.

ii. The parasympathetic division tends to have a calming effect—for example, slowing down the heartbeat and stimulating digestion.

II. Properties of Neurons (pp. 433–437)

A. Nerve cells, or neurons, have three fundamental physiological properties that enable them to communicate with other cells. (pp. 433–434)

1. Excitability. All cells are excitable, that is, they respond to stimuli. Neurons have developed this property to the highest degree.

2. Conductivity. Neurons respond to stimuli by producing electrical signals that are conducted to other cells.

3. Secretion. When the electrical signal reaches the end of a nerve fiber, the neuron secretes a neurotransmitter that stimulates the next cell.

B. Neurons fall into three functional classes based on the three major aspects of nervous system function. (p. 434) (Fig. 12.3)

1. Sensory (afferent) neurons are specialized to detect stimuli and transmit information about them to the CNS.

a. Sensory neurons begin in almost every organ of the body and end in the CNS. b. Some receptors are themselves neurons, such as those for pain and smell. In senses such as taste and hearing, the receptor is a separate cell that communicates directly with a sensory neuron.

2. Interneurons (association neurons) lie entirely within the CNS.

a. They receive signals from many other neurons and carry out integrative functions and “make decisions” about responses.

b. About 90% of neurons in the human body are interneurons.

c. The word interneuron refers to the fact that they lie between, and interconnect, the incoming sensory pathways and the outgoing motor pathways of the CNS.

Saladin Outline Ch.12

3. Motor (efferent) neurons send signals predominantly to muscle and gland cells. They are called motor neurons because most of them lead to muscle cells, and efferent neurons because they carry signals away from the CNS.

C. A motor neuron of the spinal cord illustrates the general structure of a neuron. (pp. 434–437) (Fig. 12.4)

1. The control center is the soma, also called the neurosoma or cell body. a. It contains a centrally located nucleus with a large nucleolus.

b. The cytoplasm contains mitochondria, lysosomes, a Golgi complex, many inclusions, and an extensive rough ER and cytoskeleton.

c. The cytoskeleton consists of a dense mesh of microtubules and neurofibrils (bundles of actin filaments), which compartmentalize the rough ER into dark- staining Nissl bodies. (Fig. 12.4e)

i. Nissl bodies are unique to neurons and help identify them in tissue sections.

d. Mature neurons do not divide but have long lives. Stem cells in the CNS, however, can divide and develop into new neurons.

e. The major cytoplasmic inclusions are glycogen granules, lipid droplets, melanin, and a golden brown pigment called lipofuscin.

i. Lipofuscin is produced when lysosomes digest worn-out organelles and other products.

ii. Lipofuscin accumulates with age and pushes the nucleus to one side of the cell. Granules of lipofuscin are called “wear-and-tear granules.”

2. The soma gives rise to a few thick processes that branch into a vast number of dendrites.

a. Dendrites are the primary site for receiving signals from other neurons. b. Their number varies from one to thousands, depending on the neuron.

c. As tangled as multiple dendrites may seem, they provide highly precise pathways for the reception and processing of information.

3. The axon (nerve fiber) originates on a mound on the soma called the axon hillock. a. The axon is cylindrical and relatively unbranched for most of its length, although it may give rise to axon collaterals along the way.

b. Most axons branch extensively at their distal end.

c. An axon is specialized for rapid conduction of nerve signals to points remote from the soma.

i. Its cytoplasm is the axoplasm and its membrane is the axolemma. ii. A neuron never has more than one axon, and some have none.

d. Somas range from 5 to 135 μm in diameter, while axons range from 1 to 20

μm in diameter and from a few millimeters to more than a meter in length.

e. At the distal end, an axon usually has a terminal arborization (an extensive complex of fine branches).

i. Each branch ends in a synaptic knob (terminal button) that forms a junction (synapse) with the next cell.

ii. The synapse contains synaptic vesicles full of neurotransmitter. iii. In autonomic neurons, the axons has numerous beads called varicosities. (Fig. 11.20)

4. Neurons vary in structure, and they are classified according to the number of processes extending from the soma. (Fig. 12.5)

a. Multipolar neurons are those with one axon and multiple dendrites; they are the most common type.

b. Bipolar neurons have one axon and one dendrite; examples include olfactory cells, neurons of the retina, and sensory neurons of the ear.

c. Unipolar neurons have only a single process leading away from the soma. They are represented by the neurons that carry sensory signals to the spinal cord.

i. They are also called pseudounipolar because they start out embryonically as bipolar neurons but their two processes fuse as the neuron matures.

ii. A short distance from the soma, the process branches like a T, with a peripheral fiber bringing signals from a source of sensation and a central fiber continuing into the spinal cord.

iii. The dendrites are the short receptive endings. The rest of the fiber is considered to be the axon because of the presence of myelin and the ability to produce action potentials.

d. Anaxonic neurons have multiple dendrites but no axon. They communicate through their dendrites and do not produce action potentials; some are found in the brain, retina, and adrenal medulla.

D. Axonal transport refers to the passage of proteins, organelles, and other materials along an axon, to and from the cell soma. (p. 437)

1. Movement away from the soma down the axon is called anterograde transport, and movement up the axon toward the soma is called retrograde transport.

2. Materials travel along microtubules of the cytoskeleton.

3. The motor protein for anterograde transport is kinesin; the motor protein for retrograde transport is dynein. They act somewhat like the myosin heads of muscle to crawl along

the microtubules.

4. The two types of axonal transport are fast and slow.

a. Fast axonal transport occurs at a rate of 20 to 400 mm/day and may be anterograde or retrograde.

i. Fast anterograde transport moves mitochondria, synaptic vesicles, other organelles, components of the axolemma, calcium ions, enzymes, etc. toward the distal end of the axon.

ii. Fast retrograde transport returns used synaptic vesicles to the soma and informs the soma of conditions at the axon terminals.

iii. Some pathogens, such as tetanus toxin and certain viruses, invade the nervous system by entering the distal tips of axons and traveling to the soma by fast retrograde transport.

b. Slow axonal transport is an anterograde process that works in a stop-and-go manner. It occurs at a rate of 0.5 to 10 mm/day.

i. Slow axonal transport moves enzymes and cytoskeletal components down the axons, renews worn-out axoplasmic components in mature neurons, and supplies new axoplasm for developing or regenerating neurons.

ii. Damaged nerve fibers regenerate at a speed governed by slow axonal transport.

III. Supportive Cells (Neuroglia) (pp. 438–443)

A. Neurons are outnumbered by as much as 10 to 1 by cells called neuroglia, or glial cells. Glia means “glue,” and one of the roles of these cells is to bind neurons and form a supportive framework. (p. 438)

B. There are six types of neuroglia, each of which has a unique function; four types occur only in the CNS (pp. 438–439) (Fig. 12.6) (Table 12.1)

1. Oligodendrocytes somewhat resemble an octopus with as many as 15 armlike processes.

a. Each process spirals around a nerve fiber like electrical tape, wrapping the fiber with the insulating myelin sheath.

b. This sheath speeds up nerve conduction in the CNS.

2. Ependymal cells resemble a cuboidal epithelium lining internal cavities of the brain and spinal cord. However, they have no basement membrane and have rootlike processes that penetrate into the underlying tissues.

a. Ependymal cells produce cerebrospinal fluid (CSF), which bathes the CNS

and fills its internal cavities.

b. These cells have cilia that help to circulate CSF.

3. Microglia are small macrophages that develop from white blood cells called monocytes. They wander through the CNS, constantly probing for cellular debris or other problems.

a. They are thought to perform a complete checkup on the brain tissue several times a day, phagocytizing dead tissue, microorganisms, and other foreign matter.

b. They become concentrated in areas damaged by infection, trauma, or stroke, and pathologists look for clusters in brain tissue as a clue to injury.

4. Astrocytes are the most abundant glia in the CNS and constitute over 90% of the tissue in some brain areas. They are named for their many-branched starlike shape. They have the most diverse functions of any glia.

a. They form a supportive framework for nervous tissue.

b. They have extensions called perivascular feet, which contact blood capillaries and stimulate them to form a tight seal called the blood–brain barrier.

c. They monitor neuronal activity and regulate blood flow to meet changing neuronal demand for oxygen and nutrients.

d. They convert blood glucose to lactate and supply it to the neurons. e. They secrete nerve growth factors that regulate nerve development.

f. They communicate electrically with neurons and influence synaptic signaling. g. They regulate the chemical composition of the tissue fluid, absorbing neurotransmitters and potassium ions so that they do not reach excessive levels. h. They form hardened scar tissue when neurons are damaged, a process called astrocytosis or sclerosis.

Insight 12.1 Glial Cells and Brain Tumors

5. Schwann cells, or neurilemmocytes, envelope nerve fibers of the PNS.

a. The Schwann cell winds repeatedly around a nerve fiber, producing a myelin sheath similar to the one produced by oligodendrocytes in the CNS.

b. Schwann cells also assist in regeneration of damaged fibers.

6. Satellite cells surround the somas in ganglia of the PNS; they provide electrical insulation around the soma and regulate the chemical environment.

C. The myelin sheath is a spiral layer of insulation around a nerve fiber. (p. 440)

1. Because myelin is the plasma membrane of glial cells, its composition is like that of the membrane with about 20% protein and 80% mixed lipids.

2. Production of the myelin sheath is called myelination. It begins in the fourteenth week of fetal development, proceeds rapidly in infancy, and isn’t completed until late adolescence.

a. Children under 2 years old should not be put on low-fat diets because this could interfere with myelination.

3. In the PNS, a Schwann cell spirals repeatedly around a single nerve fiber, laying down up to 100 compact layers of its own membrane with almost no cytoplasm.

(Fig. 12.7a)

a. The Schwann cell spirals outward, finally ending with a thick outermost coil called the neurilemma, which contains the body of the Schwann cell with its nucleus and most of its cytoplasm.

b. External to the neurilemma is a basal lamina and then a thin sleeve of fibrous connective tissue called the endoneurium.

4. In the CNS, each oligodendrocyte reaches out to myelinate several nerve fibers in its immediate vicinity. (Fig. 12.7b)

a. Since it is anchored to multiple nerve fibers, it cannot migrate around them, so it pushes newer layers of myelin under the older ones.

b. Myelination spirals inward toward the nerve fiber.

c. Nerve fibers of the CNS have no neurilemma or endoneurium.

5. In both the PNS and CNS, many Schwann cells or oligodendrocytes are needed to cover a single nerve fiber.

a. The myelin sheath is therefore segmented, and the gaps between the segments are called the nodes of Ranvier.

b. The myelin-covered segments from one gap to the next are called internodes and they are 0.2 to 1.0 mm long. (Fig. 12.4a)

c. The short section of nerve fiber between the axon hillock and the first glial

cell is called the initial segment. The axon hillock plus initial segment constitute the trigger zone.

D. Many nerve fibers in the CNS and PNS are unmyelinated, but in the PNS, even unmyelinated fibers are enveloped in Schwann cells. (p. 440)

1. One Schwann cell harbors from 1 to 12 small unmyenlinated fibers in grooves in its surface. (Fig. 12.8)

a. The Schwann cell’s plasma membrane does not spiral around the fiber, but folds once and somewhat overlaps at the edges.

i. This wrapping is the neurilemma.

b. Most nerve fibers travel through individual channels, but small fibers are sometimes bundled.

c. A basal lamina surrounds the entire Schwann cell and fibers.

E. The speed at which nerve signals are conducted along a nerve fiber depends on the diameter of the fiber and the presence or absence of myelin. (pp. 440–442)

1. Signal conduction occurs along the surface of a fiber, not in the axoplasm.

Insight 12.2 Diseases of the Myelin Sheath

2. Large fibers have more surface area and conduct more rapidly than small fibers.

a. Nerve signals travel about 0.5 to 2.0 m/s in small unmyelinated fibers and 3 to

15 m/s in myelinated fibers of the same size.

b. In large myelinated fibers, nerve signals travel as fast as 120 m/s.

3. Slow unmyelinated fibers are sufficient for many processes. Fast myelinated fibers occur where speed is vital, such as in motor commands to skeletal muscles.

F. Nerve fibers of the PNS are vulnerable to trauma, but may regenerate if its soma is intact and at least some neurilemma remains. (p. 443) (Fig. 12.9)

1. The regeneration process in a somatic motor neuron may be conceptualized as having the following steps:

a. When a nerve fiber is cut, the fiber distal to the injury cannot survive because it cannot synthesize protein.

i. Protein-synthesizing organelles are limited to the soma. ii. Schwann cells of the distal fiber also degenerate.

iii. Macrophages clean up tissue debris at the point of injury and beyond.

b. The soma also undergoes abnormalities.

i. The soma swells and its ER breaks up, so the Nissl bodies disperse. ii. The nucleus moves off center.

iii. Some neurons die at this stage.

c. The axon stump may sprout multiple growth processes while the distal end degenerates.

d. Muscle fibers deprived of nerve supply shrink, a process called denervation atrophy.

e. Near the injury, Schwann cells, the basal lamina, and the neurilemma form a regeneration tube.

i. Schwann cells produce cell-adhesion molecules and nerve growth factors that enable a neuron to regrow.

ii. When one growth process finds its way into the tube, it grows rapidly (3–5 mm/day) and the others are retracted.

f. The regeneration tube guides the growing sprout back to the original target cells, reestablishing synaptic contact.

g. When contact is established, the soma shrinks and returns to its original appearance, and the reinnervated muscle fibers regrow.

2. Regeneration is not perfect, as some nerve fibers may connect to the wrong muscle fibers or never find a muscle fiber. Some damaged motor neurons simply die.

3. Nerve injury is therefore often followed by some degree of functional deficit.

4. Damaged nerve fibers in the CNS cannot regenerate at all, but being enclosed in bone results in fewer traumas to the CNS.

IV. Electrophysiology of Neurons (pp. 443–451)

A. Santiago Ramon y Cajal demonstrated in the late 1800s that the nervous pathway is not a continuous “wire” or tube, but a series of cells separated by gaps that we now call synapses. (p. 443)

B. Two key issues in neurophysiology are:

1. How does a neuron generate an electrical signal?

2. How does it transmit a meaningful message to the next cell?

Insight 12.3 Nerve Growth Factor—From Home Laboratory to Nobel Prize (Fig. 12.10)

C. An electrical potential is a difference in the concentration of charged particles between one point and another. An electrical current is a flow of charged particles from one point to another. (pp. 443–445).

1. As long as a battery has an electrical potential, it is polarized.

2. Living cells are polarized because a charge difference, the resting membrane potential

(RMP), exists across the plasma membrane.

a. The membrane potential is –70 mV in a “resting” neuron. The negative value means more negative charges are on the inside of the membrane than on the outside.

3. Electrical currents in the body are created by the flow of ions such as Na+ and K+

through gated channels.

D. The resting membrane potential exists because electrolytes are unequally distributed between the extracellular fluid (ECF) and the intracellular fluid (ICF). (pp. 444–445)

1. Three factors collectively determine the RMP:

a. Diffusion of ions down their concentration gradients through the membrane. b. Selective permeability of the membrane, allowing some ions to pass more easily than others.

c. Electrical attraction of cations and anions to each other.

2. Potassium ions (K+) have the greatest influence on RMP, because the plasma is more permeable to K+ than to any other ion.

a. Many cytoplasmic anions cannot escape from the cell because of their size or charge, so that diffusion of K+ out of the cell down its concentration gradient leaves the ICF with a net negative charge. (Fig. 12.11)

b. The negative ICF attracts K+ back into the cell and eventually equilibrium is reached between concentration-driven diffusion and electrical attraction, resulting in no further net diffusion of K+.

i. At equilibrium, K+ is 40 times as concentrated in the ICF as in the

ECF.

ii. If K+ were the only ion involved, the RMP would be about –90 mV.

3. Sodium ions (Na+) also influence the RMP.

a. Na+ is 12 times more concentrated in the ECF than in the ICF.

b. Although the resting membrane is less permeable to Na+, it does diffuse down its concentration gradient into the cell and is attracted by the anions of the ICF. (Fig. 12.11)

4. The Na+–K+ pump continually compensates for the leakage of Na+ and K+ into and out

of the cell.

a. For every 1 ATP consumed by the Na+–K+ pump, 3 Na+ are pumped out of the cell and 2 K+ are brought in.

b. The Na+–K+ pump accounts for about 70% of the ATP requirement of the nervous system and it works continually, which is why the nervous system consumes so much glucose and oxygen.

5. The net effect of K+ diffusion outward, Na+ diffusion inward, and the action of the

Na+–K+ pump is the RMP of –70 mV.

E. Local changes in membrane potential occur when a neuron is stimulated. (pp. 445–446)

1. Typically, a neuron’s response begins at the dendrite, spreads through the soma, travels down the axon, and ends at the synaptic knobs. (Fig. 12.12)

2. A stimulus at the dendrite binds to receptors that open Na+ gates in the membrane so

that Na+ flows into the cell, neutralizing some of the negative charge.

a. Any change that shifts the membrane voltage to a less negative value is termed depolarization.

3. Incoming Na+ ions diffuse for a short distance and produce a current (local potential)

that travels from the stimulus point toward the cell’s trigger zone.

4. Four characteristics distinguish local potentials from action potentials. (Table 12.2)

a. Local potentials are graded, meaning that they vary in magnitude depending on the strength of the stimulus.

b. Local potentials are decremental, meaning that they get weaker as they spread from the point of stimulation.

c. Local potentials are reversible if stimulation ceases.

d. Local potentials can be either excitatory or inhibitory. The result of inhibitory local potentials is hyperpolarization (increase in negative potential).

F. An action potential is a rapid up-and-down shift in membrane voltage produced by voltage- gated ion channels in the plasma membrane. (pp. 446–449) (Fig. 12.13)

1. Action potentials occur only when there is a high enough density of voltage-gated channels; most of the soma cannot generate action potentials.

a. The trigger zone contains 350 to 500 voltage-gated channels per μm2,

compared to 50 to 75 gates per μm2 in most of the soma.

2. If a local potential spreads all the way to the trigger zone and is still strong enough, it can open the channels and generate an action potential.

3. The sequence of events in an action potential is as follows. (Fig. 12.14)

a. The current arrives at the axon hillock and depolarizes the membrane as a local potential.

b. The local potential must rise to the threshold (about –55 mV) to open the voltage-gated channels.

c. The neuron produces an action potential. The voltage-gated Na+ channels

open quickly, while K+ gates open more slowly, and the membrane depolarizes further in a positive feedback cycle.

d. As the rising membrane potential passes 0 mV, Na+ channels are inactivated

and begin closing. By the time they all close, the voltage peaks at about

+35 mV.

e. By the time the voltage peaks, the slow K+ gates are fully open, and K+ now exits the cell, which acts to repolarize the membrane.

f. K+ channels stay open longer than Na+ channels, so slightly more K+ leaves

the cell than the amount of Na+ that entered. The membrane voltage drops to 1 or 2 mV more negative than the original RMP, a condition called hyperpolarization (or afterpotential).

g. During hyperpolarization, Na+ diffusion into the cell and (in the CNS) the

removal of extracellular K+ by astrocytes gradually restore the RMP.

4. Only about one ion in a million crosses the membrane to produce an action potential, and an action potential affects distribution only in a thin layer near the membrane.

5. Action potentials differ from local potentials in the following ways. (Table 12.2)

a. Action potentials follow an all-or-none law and are not graded; if threshold is not reached, no action potential is generated.

b. Action potentials are nondecremental; they do not get weaker with distance. c. Action potentials are irreversible; once initiated, an action potential goes to completion and cannot be stopped.

G. During an action potential and for a few milliseconds after, the neuron cannot be stimulated to fire again. This period is called the refractory period. (pp. 448–449)

1. The refractory period has two phases: an absolute refractory period and a relative refractory period. (Fig. 12.15)

a. During the absolute refractory period, no stimulus of any strength will trigger a new action potential. This period lasts from the start of the action potential until the return to RMP (i.e., for as long as the Na+ channels are open).

b. During the relative refractory period, an especially strong stimulus will trigger a new action potential. This period lasts until hyperpolarization ends (i.e., for as long as the K+ channels are still open).

2. Only a small patch of membrane where an action potential has already begun is in the refractory period, not the entire neuron.

H. Signal conduction is somewhat different in unmyelinated fibers compared to conduction in myelinated fibers. (pp. 459–450)

1. An unmyelinated fiber has voltage-gated channels along its entire length. (Fig. 12.16)

a. When an action potential occurs at the trigger zone, Na+ enters the axon and

the resulting depolarization excites voltage-gated channels immediately distal to the action potential.

b. This chain reaction continues to the end of the axon.

c. An action potential does not travel along an axon, but rather, it stimulates the production of a new action potential just ahead of it.

i. An action potential is therefore different from a nerve signal, which is a traveling wave of excitation produced by the self-propagation of action potentials.

ii. No one action potential travels to the end of an axon; a nerve signal is a chain reaction of action potentials.

d. Action potentials do not travel backward because the membrane behind the nerve signal is still in its refractory period.

e. A nerve signal is not like a current in a wire; it moves much more slowly, and the last action potential has the same voltage as the first one.

2. In myelinated fibers, voltage-gated ion channels are scarce in the myelin-covered internodes (fewer than 25/μm2 compared with 2,000 to 12,000/μm2 in the nodes of Ranvier).

a. A nerve signal travels through an internode as Na+ diffuses down the fiber

under the axolemma; this flow is very fast but decremental. (Fig. 12.17a)

b. A node of Ranvier occurs every millimeter or less along the axon, however, with an abundance of voltage-gated channels.

c. When the diffusing ions reach a node, these channels are opened and a new action potential is generated, creating the impression that the nerve signal is jumping from node to node. This mode of conduction is called saltatory conduction. (Fig. 12.17b)

d. Saltatory conduction is the reason why myelinated fibers transmit signals at

120 m/s as compared to 2 m/s in unmyelinated fibers.

V. Synapses (pp. 451–457)

A. A synapse exists at the end of an axon. In synapses between two neurons, the first neuron is the presynaptic neuron (releases neurotransmitter) and the second is the postsynaptic neuron (responds to neurotransmitter). (p. 451) (Fig.12.18a)

B. A presynaptic neuron may form an axodentritic, axosomatic, or axoaxonic synapse.

(p. 451) (Fig. 12.18b)

C. A single neuron may have an enormous number of synapses. For example, a spinal motor neuron is covered with about 10,000 synaptic knobs from other neurons, and a neuron of the cerebellum may have as many as 100,000 synapses. (p. 453) (Fig. 12.19)

D. The first neurotransmitter discovered was acetylcholine, which Otto Loewi detected experimentally in 1921. (p.453)

1. Electrical communication between cells was not considered possible because of the synaptic cleft. However, we now know that some excitatory cells, such as cardiac muscle, have electrical synapses via gap junctions.

2. Most other synapses are chemical synapses relying on neurotransmitters.

E. The structure of a chemical synapse includes the synaptic knob, a part of the presynaptic neuron that contains synaptic vesicles. (p. 453) (Fig. 12.20)

1. Many of the presynaptic neuron’s vesicles are “docked” at the membrane, while others farther away constitute a reserve pool.

2. The postsynaptic neuron has no synaptic vesicles and cannot release neurotransmitters. The membrane does contain receptor proteins and ligand-gated ion channels.

F. More than 100 confirmed or suspected neurotransmitters have been identified. (pp. 453–455) (Fig. 12.21)

1. Neurotransmitters fall into four major categories according to composition. (Table 12.3)

a. Acetylcholine, in a class by itself, is formed from acetic acid and choline. b. Amino acid neurotransmitters include glycine, glutamate, aspartate, and

γ-aminobutyric acid (GABA).

c. Monoamines (biogenic amines) are synthesized from amino acids by removal of the —COOH group. The major monoamines are epinephrine, norepinephrine,

dopamine, histamine, and serotonin. The first three are in a subclass called catecholamines.

d. Neuropeptides are chains of 2 to 40 amino acids; examples are cholecystokinin (CCK) and substance P.

i. Neuropeptides are stored in large secretory granules (dense-core vesicles).

ii. Some also function as hormones or as neuromodulators.

iii. Some are produced not only by neurons but also by the digestive tract (gut–brain peptides).

2. A given neurotransmitter may not have the same effect everywhere in the body. There are multiple receptor types for a particular neurotransmitter and it is the receptor that determines the effect a neurotransmitter has on a cell.

G. Neurotransmitters have diverse actions; three examples of different modes of action are illustrated by an excitatory cholinergic synapse, an inhibitory GABA-ergic synapse, and an excitatory adrenergic synapse. (pp.455–457)

1. An excitatory cholinergic synapse employs acetylcholine (ACh) as its neurotransmitter. The steps in transmission are as follows: (Fig. 12.22)

a. The arrival of a nerve signal at the synaptic knob opens voltage-gated calcium channels.

b. Ca2+ enters the knob and triggers exocytosis of synaptic vesicles, releasing

ACh.

c. Empty vesicles drop back into the cytoplasm to be refilled and synaptic vesicles in the reserve pool move to the active sites and release ACh.

d. ACh diffuses across the cleft and binds to ligand-gated channels, which open to allow Na+ to enter the cell and K+ to leave.

e. Na+ spreads out along the inside of the membrane producing a local voltage

shift called the postsynaptic potential; if strong and persistent enough, this triggers an action potential.

2. An inhibitory GABA-ergic synapse employs γ-aminobutyric acid as its neurotransmitter.

a. GABA is released by the presynaptic neuron and binds to ion channels in a mechanism similar to that used in cholinergic synapses.

b. The GABA receptor, however, is a chloride channel, and when it opens, Cl–

enters the cell making the resting membrane potential more negative and inhibiting neuron firing.

3. An excitatory adrenergic synapse employs norepinephrine (NE) as a neurotransmitter. Its receptor is not an ion channel but a transmembrane protein associated with a G protein in a second-messenger system. (Fig. 12.23)

a. The binding of NE to the receptor causes the G protein to dissociate from it. b. The G protein binds to adenylate cyclase, stimulating it to convert ATP to cyclic AMP (cAMP).

c. Cyclic AMP can induce several alternative effects inside the cell.

i. One effect is to produce an internal chemical that binds to a ligand- gated ion channel from inside the membrane, opening the channel.

ii. Another is to activate preexisting cytoplasmic enzymes that affect metabolism.

iii. Yet another is to induce genetic transcription, so that new enzymes are produced.

d. Although slower to respond than cholinergic and GABA-ergic synapses, adrenergic synapses have the advantage of enzyme amplification. That is, a single NE molecule can induce the formation of many cAMPs, each of which in turn can activate many molecules, and so on.

4. Synaptic events require only 0.5 ms or so from the arrival of a signal at the axon terminal to the beginning of an action potential in the postsynaptic cell. This interval is called synaptic delay.

H. Cessation of a signal occurs when neurotransmitter stops being released and when neurotransmitter already present in the synaptic cleft is removed. (pp. 456–457)

1. The cessation of action potentials in the presynaptic nerve fiber stops the release of neurotransmitter.

2. The removal of neurotransmitter from the synaptic cleft is accomplished in three ways. a. Diffusion. Neurotransmitter leaves the synapse and enters the ECF. In the CNS, astrocytes absorb it and return it to the neurons.

b. Reuptake. The synaptic knob reabsorbs amino acids and monoamines by endocytosis and breaks them down with monoamine oxidase (MAO).

c. Degradation. The enzyme acetylcholinesterase (AChE) breaks down ACh into acetate and choline, the latter of which is reabsorbed by the synaptic knob.

I. Neuromodulators are hormones, neuropeptides, and other messengers that modify synaptic transmission. (p. 457)

1. The gas nitric oxide (NO) diffuses into a postsynaptic cell and activates second- messenger pathways.

2. Neuropeptides include enkephalins and endorphins, which inhibit spinal neurons from transmitting pain signals to the brain.

VI. Neural Integration (pp. 457–464)

A. The ability of neurons to process information, store and recall it, and make decisions is called neural integration. (p. 457)

B. Neural integration is based on the postsynaptic potentials produced by neurotransmitters. (pp. 458–459)

1. Any voltage change that raises the membrane potential closer to the threshold (from an RMP of –70 mV to a threshold of –55 mV) is termed an excitatory postsynaptic potential (EPSP). (Fig. 12.24a)

2. Any voltage change that hyperpolarizes the membrane and makes it more negative than the RMP is termed an inhibitory postsynaptic potential (IPSP). (Fig. 12.24b)

3. Because of ion leakage, all neurons fire at a certain background rate even when not being stimulated; EPSPs and IPSPs only change the rate of firing.

4. Glutamate and aspartate produce EPSPs (excitatory); glycine and GABA produce IPSPs (inhibitory); and acetylcholine and norepinephrine are excitatory for some cells and inhibitory for others.

C. Summation, facilitation, and inhibition are mechanisms that influence a neuron’s integration of multiple inputs. (pp. 458–459)

1. Summation is the process of adding up ESPSs and ISPSs and responding to their net effect; it occurs in the trigger zone.

a. Summation enables the nervous system to make decisions.

b. A single action potential does not produce enough activity to lead to firing. At least 30 EPSPs are needed for a postsynaptic cell to reach threshold and fire.

c. ESPSs can be added up in two ways, which may occur simultaneously.

i. Temporal summation occurs when a single synapse generates EPSPs very quickly so that they have a cumulative effect. (Figs. 12.25a, 12.26) ii. Spatial summation occurs when EPSPs from several different synapses add up to threshold at the axon hillock. (Fig. 12.25b)

d. Neurons routinely work in groups to modify each other’s actions.

i. Facilitation is a process in which one neuron enhances the effect of another. For example, one neuron firing alone may be unable to induce firing, but the combined effort of two neurons induces firing.

ii. Presynaptic inhibition is a mechanism by which one presynaptic neuron suppresses the action of another, often by blocking transmission with an inhibitory neurotransmitter. (Fig. 12.27)

D. The way in which the nervous system converts information to a meaningful pattern of action potentials is called neural coding. (pp. 459–461)

1. The most important mechanism is the labeled line code. Each nerve fiber to the brain leads from a receptor that recognized a particular stimulus type, such as optic nerve fibers that carry signals only from light receptors in the eye.

2. Quantitative information about the intensity of a stimulus is encoded in two ways.

a. In recruitment, additional neurons are brought into play as a stimulus becomes stronger, enabling the nervous system to judge stimulus strength by which and how many neurons are firing.

b. Another mechanism depends on the fact that the more strongly a neuron is stimulated, the more frequently it fires, so that the nervous system can judge stimulus strength from the firing frequency of afferent neurons. (Fig. 12.29)

i. The absolute refractory period sets an upper limit to how often a neuron can fire.

ii. The theoretical limit of firing frequency is 2,000 action potentials per second, but the highest frequencies observed are 500 to1,000 per

second.

E. Neurons function in ensembles called neural pools, which may contain thousands to millions of interneurons. The functions of a neural pool are partly determined by its neural circuit.

(pp. 461–464)

1. Information arrives at a neural pool through one or more input neurons.

a. Within the discharge zone of an input neuron, that neuron alone can make the postsynaptic cells fire. (Fig. 12.30)

b. In a broader facilitated zone, the neuron synapses with still other neurons in the pool and can stimulate them only with the assistance of other input neurons.

2. A neural pool’s neural circuit consists of the pathways among its neurons. A wide variety of neural functions result from the operation of four principal kinds of neural circuits. (Fig. 12.31)

a. In a diverging circuit, one nerve fiber branches and synapses with several postsynaptic cells, so that input from one neuron may produce output through hundreds of neurons.

b. In a converging circuit, input from many different never fibers is funneled to one neuron or neural pool. This type of circuit allows input from different sensory systems to be evaluated, such as in maintaining balance.

c. In a reverberating circuit, neurons are stimulated in a linear fashion, but some send axon collaterals leading back to the initial neurons and restimulate them.

d. In a parallel after-discharge circuit, an input neuron diverges to stimulate several neuron chains that eventually reconverge on a single output neuron.

These chains differ in total synaptic delay, meaning that their signals arrive on the output neuron at different times.

i. There is no feedback loop, and once all neurons have fired, output ceases.

ii. The output neuron may continue to fire after the stimulus stops, as signals continue to arrive.

F. The physical basis of memory is a pathway through the brain called a memory trace (engram) in which synapses can be added, taken away, or modified. The ability of synapses to change is called synaptic plasticity. (pp. 463–464)

1. During learning, synapses in a certain pathway become modified so that signals travel more easily across them. This process is called synaptic potentiation.

2. Immediate memory, one of the three kinds of memory, is the ability to hold something in mind for just a few seconds.

a. Immediate memory is necessary for continuity of events and is especially important in reading.

b. It might be based on reverberating circuits.

3. Short-term memory (STM) lasts from a few seconds to a few hours.

a. Working memory is a form of STM that allows us to hold an idea in mind long enough to carry out an action such as calling a telephone number we just looked up. Recent evidence suggests that working memory is stored in a circuit of facilitated synapses.

b. This synaptic facilitation can be induced by tetanic stimulation, the rapid arrival of repetitive signals at a synapse.

i. Rapid arrival of signals means that Ca2+ accumulates in the synaptic

knob, causing EPSPs to become stronger and stronger.

c. Memories lasting for a few hours may involve posttetanic potentiation.

i. The Ca2+ level in the synaptic knob stays elevated for so long that another signal releases a large burst of neurotransmitter, easily exciting the postsynaptic cell.

4. Long-term memory (LTM) lasts up to a lifetime and is less limited than STM in the amount of information it can store. The two forms of LTM are declarative memory and procedural memory.

a. Declarative memory is the retention of facts and events that can be put into words.

b. Procedural memory is the retention of motor skills.

c. Some LTM involves the physical remodeling of synapses or the formation of new ones through the growth and branching of axon terminals and dendrites.

d. LTM can also involve long-term potentiation in which NMDA receptors that bind glutamate are simultaneously subjected to tetanic stimulation, allowing the entry of Ca2+ as a second messenger in pyramidal cells with three effects.

i. The neuron produces more NMDA receptors, making it more sensitive to glutamate in the future.

ii. It synthesizes proteins concerned with remodeling synapses.

iii. The postsynaptic cell sends signals back to the presynaptic cell to enhance the release of neurotransmitter.

Insight 12.4 Alzheimer and Parkinson Diseases (Fig. 12.32)

Connective Issues: Effects of the Nervous System on Other Organ Systems

Cross References

Additional information on topics mentioned in Chapter 12 can be found in the chapters listed below.

Chapter 2: Anaerobic and aerobic ATP synthesis Chapter 3: Kinesin and dynein in cilia and flagella Chapter 3: Sodium–potassium pump

Chapters 3 and 11: Gated channels in membranes Chapter 4: Complexity of the genetic code Chapter 11: Membrane potential

Chapter 11: The neuromuscular junction

Chapter 14: Parts of the brain

Chapter 14: Anatomical sites of memory

Chapter 14: Ependymal cells and cerebrospinal fluid

Chapter 14: The blood–brain barrier

Chapter 15: Different effects of a single neurotransmitter Chapter 15: Drugs that inhibit monoamine oxidase Chapter 16: Role of enkephalins

Chapter 26: Action of neurotransmitters on food cravings